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Biomedical subjects

Paul B Colditz

Publications and source records attributed to Paul B Colditz.

15 recordsLinked to original sources

Hypoxic/Ischemic models in newborn piglet: comparison of constant FiO2 versus variable FiO2 delivery.

A comparison of a constant (continuous delivery of 4% FiO2) and a variable (initial 5% FiO2 with adjustments to induce low amplitude EEG (LAEEG) and hypotension) hypoxic/ischemic insult was performed to determine which insult was more effective in producing a consistent degree of survivable neuropathological damage in a newborn piglet model of perinatal asphyxia. We also examined which physiological responses contributed to this outcome. Thirty-nine 1-day-old piglets were subjected to either a constant hypoxic/ischemic insult of 30- to 37-min duration or a variable hypoxic/ischemic insult of 30-min low peak amplitude EEG (LAEEG <5 microV) including 10 min of low mean arterial blood pressure (MABP <70% of baseline). Control animals (n = 6) received 21% FiO2 for the duration of the experiment. At 72 h, the piglets were euthanased, their brains removed and fixed in 4% paraformaldehyde and assessed for hypoxic/ischemic injury by histological analysis. Based on neuropathology scores, piglets were grouped as undamaged or damaged; piglets that did not survive to 72 h were grouped separately as dead. The variable insult resulted in a greater number of piglets with neuropathological damage (undamaged = 12.5%, damaged = 68.75%, dead = 18.75%) while the constant insult resulted in a large proportion of undamaged piglets (undamaged = 50%, damaged = 22.2%, dead = 27.8%). A hypoxic insult varied to maintain peak amplitude EEG <5 microV results in a greater number of survivors with a consistent degree of neuropathological damage than a constant hypoxic insult. Physiological variables MABP, LAEEG, pH and arterial base excess were found to be significantly associated with neuropathological outcome.

Aging↗

Seizure detection algorithm for neonates based on wave-sequence analysis.

OBJECTIVE: The description and evaluation of the performance of a new real-time seizure detection algorithm in the newborn infant. METHODS: The algorithm includes parallel fragmentation of EEG signal into waves; wave-feature extraction and averaging; elementary, preliminary and final detection. The algorithm detects EEG waves with heightened regularity, using wave intervals, amplitudes and shapes. The performance of the algorithm was assessed with the use of event-based and liberal and conservative time-based approaches and compared with the performance of Gotman's and Liu's algorithms. RESULTS: The algorithm was assessed on multi-channel EEG records of 55 neonates including 17 with seizures. The algorithm showed sensitivities ranging 83-95% with positive predictive values (PPV) 48-77%. There were 2.0 false positive detections per hour. In comparison, Gotman's algorithm (with 30s gap-closing procedure) displayed sensitivities of 45-88% and PPV 29-56%; with 7.4 false positives per hour and Liu's algorithm displayed sensitivities of 96-99%, and PPV 10-25%; with 15.7 false positives per hour. CONCLUSIONS: The wave-sequence analysis based algorithm displayed higher sensitivity, higher PPV and a substantially lower level of false positives than two previously published algorithms. SIGNIFICANCE: The proposed algorithm provides a basis for major improvements in neonatal seizure detection and monitoring.

Algorithms↗

The effect of intrapartum fetal pulse oximetry, in the presence of a nonreassuring fetal heart rate pattern, on operative delivery rates: a multicenter, randomized, controlled trial (the FOREMOST trial).

OBJECTIVE: The objective of the study was to compare operative delivery rates for nonreassuring fetal status between 2 groups of laboring women: those having conventional cardiotocograph monitoring and those having cardiotocograph monitoring plus fetal pulse oximetry. STUDY DESIGN: The intrapartum fetal oximetry prospective, multicenter, randomized, controlled trial (the FOREMOST trial) was conducted in 4 Australian maternity hospitals. The primary outcome was operative birth rates for nonreassuring fetal status. RESULTS: There was a statistically significant 23% relative risk reduction in operative delivery for nonreassuring fetal status in the fetal pulse oximetry + cardiotocograph group (n = 75 of 305, 25%), compared with those in the cardiotocograph-only group (n = 95/295, 32%) (relative risk 0.77, 95% confidence interval 0.599, 0.999, P = .048). There were no significant between-group differences in overall operative births (fetal pulse oximetry + cardiotocograph group 73%, cardiotocograph-only group 71%, relative risk 1.04, 95% confidence interval 0.94, 1.15, P = .478) or neonatal outcomes. CONCLUSION: The use of fetal pulse oximetry to augment fetal well-being assessment during labor resulted in a statistically significant reduction in the operative intervention for nonreassuring fetal status, compared with the use of conventional cardiotocograph monitoring alone. This reduction was achieved with no significant difference in neonatal outcomes.

Adult↗

Women's evaluations of their experience in a multicenter randomized controlled trial of intrapartum fetal pulse oximetry (The FOREMOST Trial).

BACKGROUND: Fetal pulse oximetry improves the assessment of fetal well-being during labor. The objective of this study was to evaluate women's satisfaction with their experience with this additional technology. METHODS: We surveyed women participating in the FOREMOST trial, a randomized controlled trial comparing the addition of fetal pulse oximetry (FPO) to conventional cardiotocograph (CTG) monitoring (intervention group), versus CTG-only (control group), in the presence of nonreassuring fetal status during labor. Our survey evaluated 3 aspects of women's experience: labor, fetal monitoring, and participation in the research. The survey was administered within a few days of giving birth and repeated 3 months later. RESULTS: No differences were found between the intervention and control groups for women's evaluations of their labor, fetal monitoring, research, or overall experiences when surveyed on both occasions. Within each study group, a small but statistically significant decline occurred in women's scores for their experience of labor and overall experience from the initial survey close to the time of giving birth, to 3 months later. The magnitude of differences in responses over time was similar for the both groups. Women were more satisfied after a spontaneous or assisted vaginal birth than after cesarean section. Length of time the research midwife was present had a significant positive effect on women's ratings of their experience several days after giving birth (p = 0.006), but no effect at 3 months. CONCLUSIONS: The addition of fetal pulse oximetry for the assessment of fetal well-being during labor did not affect childbearing women's perceptions of fetal monitoring or their labor. Women evaluated their experience in the research process positively overall. Small changes occurred in women's perception of their satisfaction over time.

Adult↗

Clinicians' evaluations of fetal oximetry sensor placement in a multicentre randomised trial (the FOREMOST trial).

BACKGROUND: Fetal pulse oximetry (FPO) may improve the assessment of the fetal well-being in labour. Reports of health-care provider's evaluations of new technology are important in the overall evaluation of that technology. AIMS: To determine doctors' and midwives' perceptions of their experience placing FPO sensors. METHODS: We surveyed clinicians (midwives and doctors) following placement of a FPO sensor during the FOREMOST trial (multicentre randomised trial of fetal pulse oximetry). Clinicians rated ease of sensor placement (poor, fair, good and excellent). Potential influences on ease of sensor placement (staff category, prior experience in Birth Suite, prior experience in placing sensors, epidural analgesia, cervical dilatation and fetal station) were examined by ordinal regression. RESULTS: There were 281 surveys returned for the 294 sensor placement attempts (response rate 96%). Sensors were placed by midwives (29%), research midwives (48%), registrars (22%) and obstetricians (1%). The majority of clinicians had 1 or more years' Birth Suite experience, had placed six or more sensors previously, and rated ease of sensor placement as good. Advancing fetal station (P < 0.001) and the presence of epidural analgesia prior to sensor placement (P = 0.029) predicted improved ease of sensor placement. Having a clinician placing a sensor for the first time predicted a lower rating for ease of sensor placement (P = 0.001), compared to having placed one or more sensors previously. CONCLUSIONS: Clinicians with varying levels of Birth Suite experience successfully placed fetal oxygen saturation sensors, with the majority rating ease of sensor placement as good.

Adult↗

NSE and S100 after hypoxia in the newborn pig.

Perinatal asphyxia is an important cause of neonatal morbidity and mortality. There is the potential to halt cerebral damage if neural rescue strategies are applied within a short period of time after an insult. It is therefore important to be able to accurately identify neonates who may benefit from neural rescue therapies. Recent studies in asphyxiated neonates have correlated S100B and NSE with outcome; however, interpretation of these studies were difficult, as the timing of the measurements were not consistent. We measured NSE and S100 in 1-d-old piglets after a mild or severe hypoxic insult. Measurements were performed at 6-72 h after the insult and correlated with histologic outcome. There were no differences of the NSE or S100 concentrations between controls and the mild hypoxia group. After 24 h, there was a significant difference of NSE between the control/mild insult group and severe insult group. After 48 h, the S100 concentrations were significantly different between the control/mild insult group and the severe insult group. Both proteins showed good correlation at these time points with outcome as measured by histology score at 72 h. In conclusion, NSE and S100B measured in the serum of piglets after hypoxia increased significantly and correlated with outcome. This increase occurs too late to be used within the first 24 h but might be helpful for the clinician in determining the timing of an insult.

Animals↗

Glial glutamate transporter expression patterns in brains from multiple mammalian species.

It is generally assumed that rodent brains can be used as representative models of neurochemical function in other species, such as humans. We have compared the distributions of the predominant glial glutamate transporters in rodents, rabbits, cats, pigs, monkeys, and humans. We identify similarities but also significant differences between species. GLT-1v, which is abundantly expressed by rodent astrocytes, is expressed only in a rare subset of astrocytes of cats and humans, and appears to be absent from brains of rabbits and monkeys. Conversely, in the pig brain GLT-1v is expressed only by oligodendrocytes. GLAST and GLT-1alpha expression differed significantly between species; while rodents and rabbits exhibited uniform expression patterns in cortex, higher species, including cats, pigs, monkeys, and humans, exhibited heterogeneities in cortical and hippocampal expression. Patches devoid of labeling intermingling with patches of strong labeling were evident in areas such as temporal cortex and frontal cortex. In addition, we noted that in human motor cortex, there were inconsistencies in labeling for the C-terminal of GLT-1alpha and common domains of GLT-1, suggesting that the C-terminal region may be missing or that an unidentified splicing is present in many human astrocytes. Collectively our data suggest that assumptions as to the roles of glutamate transporters in any species may need to be tested empirically.

Aged↗

Parents' evaluation of developmental status in children born with a birthweight of 1250 g or less.

OBJECTIVE: To evaluate the agreement between parental reporting of development of children born very preterm using the Parents' Evaluation of Developmental Status (PEDS) questionnaire and professional assessment by a paediatric developmental team in the detection of sensorineural disability. METHODS: A cross-sectional cohort study of 362 children born in Queensland with a birthweight < or = 1250 g, who were surviving at 2 and 4 years of age corrected for prematurity, was conducted. Parents completed the PEDS questionnaire prior to their child receiving a neurodevelopmental assessment. The level of agreement for sensorineural disability between the neurodevelopmental assessment and the parents' score on the PEDS questionnaire was measured using the kappa statistic, and screening test characteristics were calculated. Logistic regression was used to investigate factors that might affect agreement. RESULTS: Two hundred and eighty-three (78%) of the eligible children were located and contacted. Of these, 216 (76%) agreed to participate in the study (110, 2-year-olds; 106, 4-year-olds). Agreement between the two forms of rating sensorineural disability (developmental quotient > -2SD (standard deviation), cerebral palsy, bilateral blindness and deafness requiring aids) for the 4-year age group children was fair (kappa = 0.27, P = 0.001). PEDS accurately identified 69% (11 of 16) of disabled children and 72% (65 of 90) non-disabled children. The test characteristics for these children were similar to Glascoe's norming sample with a PPV 31% (95% CI: 14-48%), specificity 72% (95% CI: 62-81%), but lower sensitivity 69% (95% CI: 62-81%) and higher false-negative rate 31% (95% CI: 11, 59). Agreement for the 2-year age group was fair with poor test characteristics. Other comparisons for both age groups (PEDS A and B compared using a disability status with DQ > -1SD) showed poor agreement and test characteristics. Gestation age < 27 weeks and maternal education at or below grade 10 in the 2-year age group were the only factors independently affecting agreement. CONCLUSIONS: The agreement between parental evaluation of sensorineural disability status using PEDS and paediatrics developmental assessment in children born very preterm at 4-years corrected age for prematurity compares favourably with Glascoe's norming sample. The lower agreement seen in the 2-year age group limits the utility of PEDS to be used as a screen for disability at an age when early intervention may be useful. The PEDS questionnaire is designed and normed for the general paediatric population, and it is not clear if parents of children born very preterm may have interpreted the PEDS questionnaire in relation to their satisfaction with their child's developmental progress rather than their child's functional ability.

Child, Preschool↗

Loss of glial glutamate transporters and induction of neuronal expression of GLT-1B in the hypoxic neonatal pig brain.

The homeostasis of glutamate is critical to normal brain function; deficiencies in the regulation of extracellular glutamate are thought to be a major determinant of damage in hypoxic brains. Extracellular levels of glutamate are regulated mainly by plasmalemmal glutamate transporters. We have evaluated the distribution of the glutamate transporter GLAST and two splice variants of GLT-1 in the hypoxic neonatal pig brain using this as model of neonatal humans. In response to severe hypoxic insults, we observe a rapid loss of two glial glutamate transporters from specific brain regions, such as the CA1 region of the hippocampus, but not the dentate gyrus. The spatial distribution of loss accords with patterns of damage in these brains. Conversely, we demonstrate that hypoxia evokes the expression of a splice variant of GLT-1 in neurons. We suggest that this expression may be induced in response to elevated extracellular glutamate around these neurons, and that this splice variant may represent a useful marker for direct quantification of the extent of likely neuronal damage in hypoxic brains.

Amino Acid Transport System X-AG↗

Perioperative predictors of developmental outcome following cardiac surgery in infancy.

At 1 year we assessed the neurodevelopmental outcomes in infants undergoing cardiac surgery, seeking to explore the predictive value of perioperative markers of cerebral injury. We prospectively enrolled 47 neurodevelopmentally normal infants prior to planned cardiac surgery. Postoperative monitoring consisted of 10-channel video synchronised, continuous electroencephalography from 6 to 30 h, Doppler assessment of cerebral blood flow in the anterior cerebral artery at 1, 2, 3 and 5 h, and measurement of serum S-100B at 0 and 24 h. Neurodevelopmental assessments were performed using the second edition of the Bayley Scale of Infant Development. Follow-up at 1 year was available on 35 infants. The mean age of these patients at surgery had been 57 +/- 15 days. We observed clinical seizures in 1 patient, with 3 other patients having electroencephalographic abnormalities. At follow-up of 1 year, neurodevelopmental scores were lower than preoperative scores, with mean mental scores changing from 103 +/- 5 to 94 +/- 13 (p = 0.001), and mean motor scores changing from 99 +/- 8 to 89 +/- 20 (p = 0.004). No association was found between electroencephalographic abnormalities, reduced cerebral blood flow, or elevation of serum S-100B levels and impaired neurodevelopmental outcome at 1 year. Infants with electroencephalographic abnormalities had elevation of the levels of S-100B in the serum (p = 0.02). At 1 year of follow-up, infants undergoing cardiac surgery demonstrated a reduction in the scores achieved using the second edition of the Bayley Scale of Infant Development. They require ongoing assessment of their progress. Electroencephalographic abnormalities, cerebral blood flow, or levels of S-100B in the serum were not useful perioperative markers for predicting a poor neurodevelopmental outcome in the clinical setting.

Age Distribution↗

Effect of cooling and re-warming on cerebral and whole body electrical impedance.

Cerebral electrical impedance is useful for the detection of cerebral edema following hypoxia in newborn infants. Thus it may be useful for determining neurological outcome or monitoring treatment. Hypothermia is a promising new therapy currently undergoing trials, but will alter impedance measurements. This study aimed to define the relationship between temperature and both cerebral and whole body electrical impedance, and to derive correction factors for adjustment of impedance measurements during hypothermia. In eight anaesthetized 1-2 day old piglets rectal, tympanic and scalp temperatures were monitored continuously. Following baseline readings at a rectal temperature of 39 degrees C, piglets were cooled to 32 degrees C. Four piglets were re-warmed. Cerebral and whole body impedance were measured at each 0.5 degrees C as rectal temperature decreased. There was a strong linear relationship between both cerebral and whole body impedance and each of the temperatures measured. There was no difference in the relationship between impedance and rectal, tympanic or scalp temperatures. The relationship for impedance and rectal temperature was the same during cooling and re-warming. Using the correction factors derived it will be possible to accurately monitor cerebral and whole body fluid distribution during hypothermic treatment.

Animals↗

Cerebral impedance and neurological outcome following a mild or severe hypoxic/ischemic episode in neonatal piglets.

Multi-frequency bio-impedance has the potential to identify infants at risk of poor neurodevelopmental outcome following hypoxia by detecting cerebral edema. This study investigated the relationship between the severity of an hypoxic/ischemic episode, neurological outcome following the hypoxia and non-invasively measured cerebral bioelectrical impedance in piglets. One-day-old piglets were anaesthetised and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 3-5%. Severe hypoxia was defined as hypoxia resulting in at least 30 min of low amplitude EEG (<5 microV) as well as hypotension and acidosis. Cerebral bio-impedance was measured before, during and for up to 6 h post-hypoxia. Neurological outcome was determined by a neurology score at 24 and 48 h after hypoxia, and by histological examination of the brain at 72 h. There was no increase in cerebral impedance in control animals. Following mild hypoxia cerebral impedance increased transiently. Following severe hypoxia, cerebral impedance increased and remained elevated. Cerebral impedance following severe hypoxia was significantly higher than after mild hypoxia at 10 min and from 2 to 6 h after resuscitation. Cerebral impedance measurements made up to 1 h and between 3 and 6 h after resuscitation were significantly correlated with neurological outcome. Results indicate that non-invasive cerebral impedance measurements are able to discriminate early between those individuals who have suffered a mild, acute hypoxic episode, and those who have suffered a severe hypoxic episode. The technique has the potential to predict which individuals will have a poor neurological outcome.

Animals↗

Noninvasive measurement of cerebral bioimpedance for detection of cerebral edema in the neonatal piglet.

The association of sustained cerebral edema with poor neurological outcome following hypoxia-ischaemia in the neonate suggests that measurement of cerebral edema may allow early prediction of outcome in these infants. Direct measurements of cerebral impedance have been widely used in animal studies to monitor cerebral edema, but such invasive measurements are not possible in the human neonate. This study investigated the ability of noninvasive cerebral impedance measurements to detect cerebral edema following hypoxia-ischaemia. One-day-old piglets were anaesthetized, intubated and ventilated. Hypoxia was induced by reducing the inspired oxygen concentration to 4-6% O(2). Noninvasive cerebral bioimpedance was measured using gel electrodes attached to the scalp. Cerebral bioimpedance was also measured directly by insertion of two silver-silver chloride electrodes subdurally. Noninvasive and invasive measurements were made before, during and after hypoxia. Whole body impedance was measured to assess overall fluid movements. Intracranial pressure was measured continuously via a catheter inserted subdurally, as an index of cerebral edema. There was good agreement between noninvasive and invasive measurements of cerebral impedance although externally obtained responses were attenuated. Noninvasive measurements were also well correlated with intracranial pressure. Whole body impedance changes did not account for increases in noninvasively measured cerebral impedance. Results suggest that noninvasive cerebral impedance measurements do reflect intracranial events, and are able to detect cerebral edema following hypoxia-ischaemia in the neonate.

Animals↗

Effect of maternal epidural analgesia on fetal intrapartum oxygen saturation.

The use of maternal epidural analgesia in labor may be associated with nonreassuring fetal heart rate (FHR) patterns. Fetal oxygen saturation (FSpO2) monitoring may improve assessment of fetal well-being during this time. Mean FSpO2 values were compared over seven 5-minute epochs: 5 minutes prior to an epidural event (combined insertion of epidural/top-up epidural analgesia and infusion pump bolus), to 30 minutes following the event, including possible effects of maternal position and FHR pattern on FSpO2 values. Mean FSpO2 values were significantly different between the 5 minutes prior (49.5%) versus 16-20 minutes (44.3%, p <0.05), 21-25 minutes (43%, p <0.01), and 26-30 minutes (43.8%, p <0.05) epochs; and 6-10 minutes (48.3%) versus 21-25 minutes (43%, p <0.05) epochs, but were not influenced by FHR pattern or maternal position. There were no differences in mean FSpO2 values following administration of an epidural infusion bolus. We conclude that fetal oxygenation was affected following initial or top-up epidural analgesia and that fetal intrapartum pulse oximetry may be useful in assessing fetal status following these events.

Analgesia, Epidural↗

Update on intrapartum fetal pulse oximetry.

This article examines the current status of fetal pulse oximetry (FPO) as a means of intrapartum assessment of fetal wellbeing. FPO has been developed to a stage where it is a safe and accurate indicator of intrapartum fetal oxygenation. In general, sliding the FPO sensor along the examiner's fingers and through the cervix, to lie alongside the fetal cheek or temple is easy The recent publication of a randomised controlled trial (RCT) of FPO versus conventional intrapartum monitoring has validated its use to reduce caesarean section rates for nonreassuring fetal status. An Australian multicentre RCT is currently underway. Maternal satisfaction rates with FPO are high. FPO may be used during labour when the electronic fetal heart rate trace is nonreassuring or when conventional monitoring is unreliable, such as with fetal arrhythmias. If the fetal oxygen saturation (FSpO2) values are < 30%, prompt obstetric intervention is indicated, such as fetal scalp blood sampling or delivery FSpO2 monitoring should not form the sole basis of intrapartum fetal welfare assessment. Rather, the whole clinical picture should be considered.

Female↗